Condensation products of the sugars with derivatives of esculetol and process



Patented Nov. 4, 1952 'orso CONDENSATION PRODUCTS OF THE SUGARS WITH DERIVATIVES OF ESCULETOL AND PROCESS a corporation of France No Drawing. Application May 5, 1949, Serial No. 91,636. In France July 5, 1948 3Llaims. 1 ZIhis invention comprises osides obtained b condensation of sugars with alkyl or aryl-4 derivatives of esculetol and their preparation.

. Eseuletol or dihydroxy-6,7 coumarin is the aglycone of a natural glucoside, esculin or esculoside, havingthe formula P properties in methyl-l-esculetol, equally useful I in solar light .filters, and of which no oside has heretofore been described.

These osides .have :the general formula where R1 represents an alkyl or aryl radical, .182

an osidic radical of for example Cal-11105, and

Rs an 'atom of hydrogen, an alkyl, aryl or acyl radical, as :for example, -CH3, CsH5CH2, onaoo-, or the-reverse for R2 andRa.

The advantage presented by these osides .over

themanufactureof glucosides of esculetol is that 1 the basic matter, thealkyloraryl-4 esculetol, is

much more easily obtainable by synthesis than is esculetol itself-0f which a preparation following the method of Von Pechmann was described by G. Amiard and A. Allais (Bull. Soc. Chim, 1947, 14, 512).

The preparation of the 'alkylor aryl-xl esculetol can be effected following the method described in Organic Synthesis, collective volume 1, p. 352 for methyl-4 esculetol. The fixation of the osidi'c residue in position 7 is obtained by The fixation of the osidic residue .to the contrary takes place in position 6 when following the method concisely given by K. W. Merz and W. Hagemann (Naturwiss, 1941, 29, 650) and repeated in detail by JG. Amiard and G. Nomine (BulLSoc. Chim., 1948,, 15 476) for the preparation of esculosides zfrom-esculetol.

The differenttsteps .in the preparation of products according to the invention are the ffollowing:

One of vthe phenol groupsofthealkyhorsaryl-4 esculetol is blocked either by esterification in "position 6 or by-etherification in position '7, and the resulting product is treated with "acetyla'ted suganfor example the pentaacetyl-glucoseorone of its substituted products, a-aceto bromo"glu cose, nitro-aceto g1ucose, etc. The oside obtained is de-acetylated catalytically in an aimhollin'the presence of an alkali, or byian entirely different procedure, for example, by saponification in any aqueous or alcoholic alkaline solution. If an oside is desired in which the vsecond Phenol group is free, this functional group isi-previously blocked-by a residue readily replaceable'lby hydrogen, as for example, .a benzylgroup, CH5-VCH2-.

These novel osides 'find application in medi- :cines "for -humans and animals inasmuch as they have vitamin B properties or in solar filters -due to their power of absorbing luminous radiations.

Hereinafter there is given, by'way of example but not limited thereto, the preparation of methyl-4 fi-d-glucoepyranosidoxy-B benzyfl-oxy-T coum'arin 'or methyl-'4 es'culetol ,glu'cos'icle (6 position) benzylated in. the '7 position,- and of methyl 4B d glucopyranosidoxy I6 IhydrOXy-I'? Jcoumarin or methyl-4 esculoside. The following Formulas 1, 2 and 3 are those :of the intermediates and formulas 4 and 5 are those of @the above -mentioned products:

OCOCH:

CHaCOO 0000113 OH: I onacooo'nl HO OH (13H;

noon 0- o H CH 0 o a s 2 \O (4) E0 on out noon 0 0 I s) Example For the preparation of the above-mentioned compounds the following are the steps:

First step-Obtaining methyl-4 esculetol benzylate'd (7) (Formula 2).

There is heated to reflux during one hour 17.8 gms. of methyl-4 esculetol (Formula 1), 135 cc. of alcoholic caustic soda (3.4%), 54 cc. of water and 25 gms. of benzyl chloride, and. the alcohol is distilled under reduced pressure. The residue is extracted by means of chloroform, separating from the methyl-4 esculetol which has not reacted (4.3 gms. or 27%) the latter is filtered and washed with chloroform. The mother-chloroform solution and the washing chloroform is Washed with a solution of 10% sodium carbonate, in order to eliminate the last traces of methyl-4 esculetol, and with a normal solution of caustic soda to extract the mono-benzyl-methyl-4 esculetol'. By acidifying with hydrochloric acid the soda washing solution, there is precipitated the methyl-4' esculetol benzylated in position 7 (Formula 2), which is filtered, washed with water and dried to 80 C. After recrystallization in dichlorethane, there remains 12 gms. (46%), fusion point 200 C. (instantaneous).

Second step.-Obtaining methyl-4 esculetol tetra-acetyl-glucoside (6) benzylated (7) (Formula 3).

' Ther'eis permitted to react at room temperature'9 gms. of aceto-bromo-glucose with 5 gms. of

the benzylated (7) methyl-4 esculetol (Formula 2) dissolved in 11 cc. of ZN-caustic soda, 11 cc. of water and 45 cc. of acetone. The glucoside crystallizes. It is filtered, washed with dilute caustic soda, with water, with alcohol, and dried to 80" C. Result is 4.7 gms. (43%) fusion point 195 C. (instantaneous). (a) =19.5- 1 (pyr idine, c=3%). By acidification of the washing soda solution there is recovered .7 gms. of benzylated methyl-4 esculetol (34%).

Third step-Obtaining of methyl-4 esculetol glucoside (6) benzylated (7) (Formula 4).

Of the preceding product 4 gms. in a suspension point 170 C. (instantaneous),

(pyridine c=3%). It is insoluble in water and alkaline solutions, soluble in methanol and pyridine.

Fourth. step.0btaining of methyl-4 esculetol glucoside (6) (Formula 5). I There, is agitated in an atmosphere of hydrogen 2 gms. of methyl-4 esculetol glucoside. (6)

benzylated (7) (Formula 4) in 50 cc. of methanol 7 with 0.5 gm. palladium black (6% palladium) A rapid absorption of a moleculeof hydrogen occurs. It is heated to boiling, the palladium black is filtered and washed with boiling methanol. The methyl-4 esculoside crystallizes on cooling. It is filtered and washed with methanol.

Result: 1.30 gms. (82%) of product dried at 30 C. under vacuum and retaining one molecule of water of crystallization. It melts at C. with loss of water of crystallization (pyridine c=2 It is slightly soluble in water, methanol and alcohol, soluble in pyridine and alkaline solutions.

What is claimed is:

1. fi-glucoside of methyl-4 esculetol;

2. In a process of preparing the 6-glucoside of methyl-4-esculetol, the steps comprising blocking the 7-pheno1 group of said methyl-4-esculetol, treating the resulting reaction product with acetylated gulcose, and de-acetylating and dBbIOCk', ing the phenol group in the resulting fi-glucosido- 4-methyl esculetol compound.

3. In a process of preparing the 6-glucoside of methyl-4-esculetol by benzylation of the 7-phenol group, reactingthe resulting 7-benzylated'com pound with acetylated glucose, and de-acetylating and de-benzylating the glucoside compound formed, the step comprising heating under reflux methy1-4-esculetol in aqueous-alcoholic alkali hydroxide solution with an excess of benzylchloride to form 7-benzylmethyl-4-esculetol.

LEON VELLUZ. GASTON AMIARD.

REFERENCES CITED The following references are of record in the file of this patent: 

1. 6-GLUCOSIDE OF METHYL-4 ESCULETOL. 